Metabolomics
With the completion of the sequencing of the human genome, it has become apparent that genetic information alone is incapable of providing a comprehensive characterization of the biochemical and cellular functioning of complex biological systems. As a result, the focus of much molecular biological research is shifting toward proteomics and metabolomics, broadly defined as the systematic analysis of proteins and small molecules such as polypeptides, hormones and neurotransmitters (and their metabolites) in a physiological environment such as a biological sample, a cell, tissue, or organism. Because proteins and metabolites are far more numerous, diverse, and fragile than genes, existing tools for their discovery, identification, and quantification do not meet the needs of researchers or clinicians.
One important aspect of proteomics is the identification of proteins with inherent mutations or altered expression levels. Differences in protein and metabolite levels over time or among populations can be correlated with disease states, drug regimens, or alterations to metabolism. Identified molecular species may serve as biological markers (biomarkers) for the disease or condition in question, thereby permitting new methods of diagnosis, prognosis and disease management to be developed or more suitably tailored for the patient. In order to discover such biological markers, it is helpful to obtain accurate measurements of relative differences in protein and metabolite levels between different sample types, a process referred to as differential phenotyping.
In vitro Fertilization (IVF) Treatment
The field of assisted reproductive technologies (ART) including IVF, whether applied to humans or animals, is a somewhat inexact science or art. The ability to assess viability of spermatozoa (sperm cells), oocytes (eggs) and embryos is done essentially by visual appearance under a microscope. Visual appearance of these cells does not correlate well with viability in many cases. No other information about what is going on in the cells is available to ART specialists to guide the process. The whole procedure is performed with the hope that viable gametes will be selected and that these gametes will produce viable embryos that will successfully implant in a uterus and go on to produce healthy offspring. While genetic testing of embryos by extracting one cell is possible to determine at least some factors of viability, such an “invasive” procedure can adversely affect the embryo. No technique presently exists that allows embryologists and other ART specialists to efficiently assess the viability of these cells for ART procedures.
IVF has proven to be the most viable alternative available to infertile couples and is increasingly becoming recognized as appropriate “first line” procedure over other treatment options.
IVF procedures can be broken down into six broad procedural stages: 1) stimulation of the female using fertility hormone drugs to produce a large cohort population of oocytes; 2) retrieval of oocytes; 3) male gamete collection and preparation, followed by fertilization of the egg; 4) culturing of resulting zygotes/embryos in growth media; 5) embryo selection, and finally 6) embryo transfer. Typically, the key events comprising embryo implantation and pregnancy are not considered part of the IVF process since they are outside the control of the procedure per se. In current IVF practice, oocytes and embryos that are selected for the procedure are assumed to be viable or healthy, based primarily on subjective morphological criteria and development patterns (in the case of the embryo); no biological metrics are available to assist in this very critical selection process. Unused embryos are typically cryopreserved.
ART services now make it possible to offer treatment options also to patients who a priori are not infertile, but who wish to push back or control the “biological clock to enhance and/or preserve their reproductive function (or fertility) (fertility preservation). The application of ART services to otherwise normal, fertile population has created a new therapeutic paradigm of Fertility Preservation. The need for controlled fertility delay may be further appreciated for example if a patient is undergoing chemotherapy wherein reproductive function may be perturbed.
Today there are no practical biological criteria or analytical methods enabling selection of oocyte, sperm, or embryo to ensure efficacy or safety of the IVF procedure. Consequently, with no analytical methodologies available to reliably assess oocyte competency at the front end of the IVF procedure, embryologists have resorted to subjective and non-standardized embryo development criteria and morphology as indicators of embryo quality and, by inference, original oocyte quality.